Eitner F, Cui Y, Hudkins K L, Alpers C E
Department of Pathology, University of Washington, Seattle 98195, USA.
Transplantation. 1998 Dec 15;66(11):1551-7. doi: 10.1097/00007890-199812150-00021.
Mononuclear cell infiltration is a common feature of cell-mediated renal transplant rejection. Chemokines and their corresponding receptors likely play a central role in directing specific classes of leukocytes to graft sites during rejection. Localization of chemokine receptors may help us understand how specificity in leukocyte trafficking is achieved in renal inflammatory processes. The localization of the chemokine receptor CXCR4 in human kidney and in renal transplant rejection is unknown.
We generated a riboprobe specific for the detection of CXCR4 mRNA by in situ hybridization to evaluate cellular sites of synthesis of this receptor in native human kidneys (n=11) and in human allograft nephrectomies with features of severe rejection (n=14).
By in situ hybridization, CXCR4 mRNA expression is undetectable in intrinsic glomerular, tubular, and renovascular cells in native kidneys. When renal interstitial inflammation is present, CXCR4 mRNA expression is localized to a large fraction of infiltrating leukocytes. Large numbers of CXCR4-expressing cells are detected in cell-mediated renal allograft rejection. Double immunolabeling for CD3 antigen identified a large fraction of infiltrating CXCR4 mRNA-expressing cells as T lymphocytes. CXCR4 mRNA-expressing cells were frequently seen in neointimal lesions of vascular rejection in allograft nephrectomies. CXCR4 mRNA expression was identified in infiltrating neointimal T lymphocytes, but not smooth muscle cells by immunolabeling.
We demonstrate the involvement of CXCR4 mRNA-expressing infiltrating cells in human renal interstitial and vascular allograft rejection. Signaling via the CXCR4 receptor may be one mechanism by which chemokines mediate leukocyte trafficking in renal allograft rejection.
单核细胞浸润是细胞介导的肾移植排斥反应的常见特征。趋化因子及其相应受体可能在排斥反应期间将特定类型的白细胞导向移植部位的过程中发挥核心作用。趋化因子受体的定位可能有助于我们理解在肾脏炎症过程中白细胞运输的特异性是如何实现的。趋化因子受体CXCR4在人肾脏及肾移植排斥反应中的定位尚不清楚。
我们通过原位杂交生成了一种特异性用于检测CXCR4 mRNA的核糖探针，以评估该受体在人正常肾脏（n = 11）和具有严重排斥特征的人同种异体移植肾切除标本（n = 14）中的细胞合成部位。
通过原位杂交，在正常肾脏的固有肾小球、肾小管和肾血管细胞中未检测到CXCR4 mRNA表达。当存在肾间质炎症时，CXCR4 mRNA表达定位于大部分浸润的白细胞。在细胞介导的肾移植排斥反应中检测到大量表达CXCR4的细胞。对CD3抗原进行双重免疫标记确定大部分浸润的CXCR4 mRNA表达细胞为T淋巴细胞。在同种异体移植肾切除标本的血管排斥反应的新生内膜病变中经常可见表达CXCR4 mRNA的细胞。通过免疫标记在浸润的新生内膜T淋巴细胞中鉴定出CXCR4 mRNA表达，但在平滑肌细胞中未鉴定出。
我们证明了表达CXCR4 mRNA的浸润细胞参与了人肾间质和血管同种异体移植排斥反应。通过CXCR4受体发出信号可能是趋化因子在肾移植排斥反应中介导白细胞运输的一种机制。
